Elucidating cuproptosis-related gene SLC31A1 diagnostic and prognostic values in cancer

Jiaoping Mi; Juncong Luo; Huanwen Zeng; Hongyu Zhang; Muhammad Jamil; Mostafa A Abdel-Maksoud; Adel M Zakri; Akram A Alfuraydi; Ning Zhang; Mei Xiao

Elucidating cuproptosis-related gene SLC31A1 diagnostic and prognostic values in cancer

Am J Transl Res. 2023 Oct 15;15(10):6026-6041. eCollection 2023.

Authors

Jiaoping Mi^{1

2}, Juncong Luo³, Huanwen Zeng³, Hongyu Zhang³, Muhammad Jamil⁴, Mostafa A Abdel-Maksoud⁵, Adel M Zakri⁶, Akram A Alfuraydi⁵, Ning Zhang⁷, Mei Xiao³

Affiliations

¹ Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University Guangzhou 510080, Guangdong, PR China.
² Department of Otolaryngology Head and Neck Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University Zhuhai 519000, Guangdong, PR China.
³ Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University Zhuhai 519000, Guangdong, PR China.
⁴ PARC Arid Zone Research Center Dera Ismail Khan 29050, Pakistan.
⁵ Department of Botany and Microbiology, College of Science, King Saud University P.O. Box 2455, Riyadh 11451, Saudi Arabia.
⁶ Department of Plant Production, College of Food and Agricultural Sciences, King Saud University P.O. Box 2455, Riyadh 11451, Saudi Arabia.
⁷ Internal Medicine Oncology, Minhang Brunch Fudan University Shanghai Cancer Center Shanghai 200240, PR China.

PMID: 37969191
PMCID: PMC10641336

Abstract

Objectives: Cancer remains a global health challenge, necessitating the identification of novel biomarkers and therapeutic targets. Cuproptosis, a recently recognized form of cell death linked to copper metabolism, presents a promising avenue for anticancer strategies. We investigated the clinical significance of SLC31A1, a key regulator of cuproptosis, in multiple cancer types, aiming to elucidate its potential as a diagnostic biomarker, prognostic, indicator and therapeutic target.

Methods: We conducted a pan-cancer analysis through TIMER2.0, evaluating SLC31A1 expression across multiple cancer types. Survival analysis was performed using KM plotter. Expression validation was carried out using UALCAN and Human Protein Atlas (HPA) databases. Methylation analysis was conducted with the help of ULACAN and OncoDB. Mutational analysis was performed using cBioPortal database. Immune infiltration analysis via the TIMER2.0 and gene enrichment analysis via the Metascape were performed to gain insights into the potential mechanisms underlying SLC31A1's role in cancer. Finally, Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to confirm SLC31A1 expression in clinical samples.

Results: Out of analyzed cancer, SLC31A1 exhibited significant up-regulation and correlation with worse overall survival (OS) across Breast Cancer (BRCA), Cervical Squamous Cell Carcinoma (CESC), Head and Neck Squamous Cell Carcinoma (HNSC), and Esophageal Carcinoma (ESCA). Mutational and promoter methylation analyses further revealed that hypomethylation is the major cause of SLC31A1 overexpression among BRCA, CESC, HNSC, and ESCA. Immune infiltration analysis showed significant associations between SLC31A1 expression and the presence of CD8+ T cells, CD4+ T cells, and macrophages in the tumor microenvironment. Gene enrichment analysis provided valuable insights into potential molecular pathways in context to BRCA, CESC, HNSC, and ESCA. Furthermore, when SLC31A1 was analyzed using clinical samples through RT-qPCR, this gene showed promising diagnostic potential, reflected by high Area Under the Curve (AUC) values.

Conclusion: Our pan-cancer study highlights the up-regulation of SLC31A1 and its correlation with worse OS in BRCA, CESC, HNSC, and ESCA. In sum, outcomes of this study showed that SLC31A1 could be a potential biomarker and novel therapeutic target of BRCA, CESC, HNSC, and ESCA.

Keywords: SLC31A1; biomarker; pan-cancer analysis.